Gut Barrier Function
The intestinal barrier provides protection from potentially harmful agents in the intestinal lumen, while allowing absorption of nutrients. Several mechanisms are involved in gut barrier function, such as intestinal morphological structure, systemic and local inflammation, intestinal bacterial translocation, and gut resistance. Gut barrier integrity may be compromised or disrupted during processes of intestinal inflammation, infection, allergic sensitization as well as a number of autoimmune diseases. More specifically, these mechanisms are potentially impaired in preterm and/or low birth weight infants, suffering from infections, congenital intestinal malformations, necrotizing enterocolitis (NEC) and short bowel syndrome (SBS).
Infections, such as rotavirus, and villous atrophy caused by, for example celiac disease, can lead to altered intestinal barrier properties. Impaired gut barrier function may result in reduction of villous height and increased crypt depth. SBS is defined as the malabsorptive state when the functioning gut mass is reduced below the amount necessary for adequate digestion and absorption of food and fluid that eventually leads to clinical nutrient deficiencies and requires parenteral nutrition (PN) support. Some children are born with a congenital short bowel, while others acquire it surgically, for example for surgical treatment of necrotizing enterocolitis. SBS is a leading cause of intestinal failure in neonates, infants and young children, with high prevalence in premature infants. Intestinal bacterial overgrowth and bacterial translocation is a major complication of SBS, and is caused by disrupted gut barrier function.
As suggested by animal and clinical studies, intestinal bacterial overgrowth and translocation in infants with impaired gut barrier function may not only be a factor involved in gut-derived infection, but also may further impair the rehabilitation process. It also may impair gut regeneration, maturation, differentiation, and epithelial functioning. The aforementioned impairments can result in malabsorption. Intestinal gut flora also contribute to a healthy and intact gut barrier due to their metabolic, trophic, and immune modulatory properties.
Probiotics may be helpful in pediatric patients with impaired gut barrier function due to any of the aforementioned causes. Nevertheless, the administration of viable bacteria to pediatric subjects, and particularly preterm infants, with impaired intestinal defenses and immature gut barrier function may not be feasible due to the risk of bacteremia. Moreover, soluble factors secreted from viable probiotic material may be involved in some of the beneficial effects of probiotic bacteria. Therefore, there is a need for compositions that can provide the benefits of probiotics without introducing viable bacteria into the intestinal tract of pediatric subjects suffering from impaired/immature gut barrier function, such as SBS or NEC.
Visceral Pain Disorders in Pediatric Subjects
The early postnatal period is normally a stress-hyporesponsive period during which time there is an intense phase of neuronal growth and myelination. Stressful episodes such as food intolerance, allergic or non-allergic inflammation, colic, inflammatory bowel syndrome, and infections during this critical window can have long lasting effects starting in early life. Such effects include visceral hypersensitivity and reduced diversity of intestinal microbiota. Probiotics may be useful in reducing visceral hypersensitivity, but information on the effects of probiotic soluble mediators is lacking. Therefore, there is a need for compositions and methods for reducing visceral pain in infants and children, and in particular, pediatric groups with increased visceral sensitivity.